Role of high-dose chemotherapy and autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

Abstract


High-dose chemotherapy (HD-CT) in combination with autologous stem cell transplantation (auto-SCT) has long become the gold standard treatment for chemosensitive recurrences and refractory diffuse large B-cell lymphoma (DLBCL). By taking into account the low efficiency of rescue therapy (postrecurrence five-year survival rate is not more than 10-20%), it is clear that the results of treatment should be improved in the induction of the first remission. The study performed in the rituximab time showed the higher efficiency of first-line therapy using auto-SCT. Therapeutic effectiveness was also noted to depend on the intensity of pretransplantation regimens. Indications for HD-CT with auto-SCT must be substantiated because of the higher toxicity together with therapy intensification. Conventional clinical criteria for this are insufficient. Thus, it is necessary to search for new molecular genetic prognostic factors that will be able to portray tumor biology.

Full Text

Роль высокодозной химиотерапии и трансплантации аутологичных стволовых клеток крови у пациентов с диффузной В-крупноклеточной лимфомой. - Аннотация. Высокодозная химиотерапия (ВД-ХТ) с трансплантацией аутологичных стволовых клеток крови (ауто-ТСКК) давно стала "золотым стандартом" лечения химиочувствительных рецидивов и рефрактерных форм диффузной В-крупноклеточной лимфомы (ДВККЛ). С учетом крайне низкой эффективности терапии спасения (5-летняя выживаемость после рецидива не превышает 10-20%) становится ясно, что необходимо улучшать результаты лечения больных в индукции первой ремиссии. Исследования, выполненные в эру ритуксимаба, показали увеличение эффективности первой линии терапии с применением ауто-ТСКК. Кроме того отмечено, что эффективность терапии зависит от интенсивности предтрансплантационных режимов. Показания к проведению ВД-ХТ с ауто-ТСКК должны быть обоснованными ввиду повышения токсичности вместе с интенсификацией терапии. Общепринятых клинических критериев для этого становится недостаточно. Таким образом, необходим поиск новых молекулярно-генетических факторов прогноза, которые смогут отразить биологию опухоли.

References

  1. Воробьев А.И., Кременецкая А.М. Атлас опухолей лимфатической системы. М: Ньюамед 2007; 292.
  2. Swerdlow S., Campo E., Harris N.L. et al. International Agency for Research on Cancer. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. Geneva, Switzerland: World Health Organization 2008.
  3. Davydov M.I., Aksel E.M. Cancer statistics in Russia and CIS 2009. JOURNAL of N.N. Blokhin Russian Cancer Research Center RAMS 2011; 3 (85) suppl. 1.
  4. Pfreundschuh M., Kuhnt E., Trumper L. et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011; 12: 1013-1022.
  5. Recher C., Coiffier B., Haioun C. et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 2011; 378: 1858-1867.
  6. Philip T., Guglielmi C., Hagenbeek A. et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 1995; 333 (23): 1540-1545.
  7. NCCN Guidelines for Treatment of Non-Hodgkin Lymphoma. http://http://www.nccn.org. Accessed May 30, 2012.
  8. Kewalramani T., Zelenetz A.D., Nimer S.D. et al. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2004; 103 (10): 3684-3688.
  9. Vellenga E., van Putten W.L., Vant Veer M.B. et al. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood 2008; 111 (2): 537-543.
  10. Sieniawski M., Staak O., Glossmann J.P. et al. Rituximab added to an intensified salvage chemotherapy program followed by autologous stem cell transplantation improved the outcome in relapsed and refractory aggressive non-Hodgkin lymphoma. Ann Hematol 2007; 86 (2): 107-115.
  11. Martın A., Conde E., Arnan M. et al. R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica 2008; 93 (12): 1829-1836.
  12. Feugier P., Van Hoof A., Sebban C. et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 2005; 23 (18): 4117-4126.
  13. Pfreundschuh M., Trumper L., Osterborg A. et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomized controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 2006; 7 (5): 379-391.
  14. Fenske T.S., Hari P.N., Carreras J. et al. Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma. Biol Blood Marrow Transplant 2009; 15 (11): 1455-1464.
  15. Gisselbrecht C., Glass B., Mounier N. et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28: 4184-4190.
  16. Thieblemont C., Briere J., Mounier N. et al. The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol 2011; 29: 4079-4087.
  17. Gisselbrecht C. Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Hematology Am Soc Hematol Educ Program 2012; 2012: 410-416.
  18. Kim J.E., Lee D.H., Yoo C. et al. BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: a single center comparative analysis of efficacy and toxicity. Leuk Res 2011; 35: 183-187.
  19. Vose J.M., Carter S.L., Burns L.J. et al. Randomized phase III trial of 131iodine-tositumomab (Bexxar)/carmustine, etoposide, cytarabine, melphalan (BEAM) vs. rituximab/BEAM and autologous stem cell transplantation for relapsed diffuse large B-cell lymphoma (DLBCL): no difference in progression-free (PFS) or overall survival (OS). Blood 2011; 118: 661.
  20. Shimoni A., Avivi I., Rowe J. et al. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer 2012; 118: 4706-4714.
  21. Krishnan A., Palmer J., Tsai N.C. et al. Matched-cohort analysis of autologous hematopoietic cell transplantation with radioimmunotherapy versus total body irradiationebased conditioning for poor-risk diffuse large cell lymphoma. Biol Blood Marrow Transplant 2012; 18: 441-450.
  22. Majhail N.S., Kirsten K., Ness K.K. et al. Late effects in survivors of Hodgkin and non-Hodgkin lymphoma treated with autologous hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Biol Blood Marrow Transplant 2007; 13: 1153-1159.
  23. Gisselbrecht C., Glass B., Laurent G. et al. Maintenance with rituximab after autologous stem cell transplantation in relapsed patients with CD20+ diffuse large B-cell lymphoma (DLBCL): CORAL analysis. J Clin Oncol 2011; 29: abstr. 8004.
  24. Staudt L., Dunleavy K., Buggy L. et al. The Bruton's tyrosine kinase (Btk) inhibitor PCI-32765 modulates chronic active BCR signaling and induces tumor regression in relapsed/refractory ABC DLBCL. Blood 2011; 118: abstr. 2716.
  25. Advani A., Coif!er B., Czuczman M. et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin' s lymphoma: results of a phase I study. J Clin Oncol 2010; 28: 2085-2093.
  26. Gordon L., Weller E., Armand P. et al. A phase II study of CT-011, an anti-PD-1 antibody, after AUSCT in recurrent/refractory DLBCL: 1-rst analysis of progression-free-survival (PFS), overall survival (Os) and toxicity. Ann Oncol 2011; 22 (Suppl 4): 63 [abstract].
  27. Hofmeister C.C., Lozanski G., Baiocchi R.A. et al. Phase I Study Of Vorinostat (SAHA) After Autologous Transplant For Patients With High Risk Lymphoma. Biol Blood Marrow Transplant 2010; 16 (2): 204-205.
  28. Hitz F., Connors J., Gascoyne R. et al. Outcome of patients with chemotherapy refractory and early progressive diffuse large B cell lymphoma after R-CHOP treatment. Blood (ASH Annual Meeting Abstracts) 2010; 116 (21): 1751 [abstract].
  29. Cultrera J.L., Dalia S.M. Diffuse large B-cell lymphoma: current strategies and future directions. Cancer Control 2012; 19 (3): 204-213.
  30. van Besien K.W., Mehra R.C., Giralt S.A. et al. Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology. Am J Med 1996; 100 (3): 299-307.
  31. Jantunen E., Canals C., Rambaldi A. et al. Autologous stem cell transplantation in elderly patients (> or = 60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry. Haematologica 2008; 93 (12): 1837-1842.
  32. Lazarus H.M., Carreras J., Boudreau C. et al. Influence of age and histology on outcome in adult non-Hodgkin lymphoma patients undergoing autologous hematopoietic cell transplantation (HCT): a report from the Center For International Blood & Marrow Transplant Research (CIBMTR). Biol Blood Marrow Transplant 2008; 14 (12): 1323-1333.
  33. Птушкин В.В., Жуков Н.В., Миненко С.В. и др. Высокодозная химиотерапия с трансплантацией аутологичных клеток-предшественников гемопоэза и применением ритуксимаба (мабтера) при неходжкинских лимфомах. Соврем онкол 2006; 10 (3): 84-87.
  34. Савченко В.Г., Менделеева Л.П., Павлова О.А. и др. Трансплантация аутологичных гемопоэтических клеток у больных лимфомами. Новые технологии в клинической практике. М 1999: 60-61.
  35. Greb A., Bohlius J., Schiefer D. et al. High-dose chemotherapy with autologous stem cell transplantation in the first line treatment of aggressive non-Hodgkin lymphoma (NHL) in adults. Cochrane Database Syst Rev 2008; 1: CD004024 [abstract].
  36. Gianni A.M., Bregni M., Siena S. et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. New Engl J Med 1997; 336 (18): 1290-1297.
  37. Santini G., Salvagno L., Leoni P. et al. VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's lymphoma cooperative study group. J Clin Oncol 1998; 16 (8): 2796-2802.
  38. Gisselbrecht C., Lepage E., Molina T. et al. Shortened firstline high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma. J Clin Oncol 2002; 20 (10): 2472-2479.
  39. Kaiser U., Uebelacker I., Abel U. et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for aggressive lymphoma. J Clin Oncol 2002; 20 (22): 4413-4419.
  40. Martelli M., Gherlinzoni F., De Renzo A. et al. Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non- Hodgkin's lymphoma: an Italian multicenter randomized trial. J Clin Oncol 2003; 21 (7): 1255-1262.
  41. Olivieri A., Santini G., Patti C. et al. Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG. Ann Oncol 2005; 16 (12): 1941-1948.
  42. Vitolo U., Liberati A.M., Cabras M.G. et al. High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: an "Intergruppo Italiano Linfomi" randomized trial. Haematologica 2005; 90 (6): 793-801.
  43. Betticher D.C., Martinelli G., Radford J.A. et al. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of Non-Hodgkin Lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol 2006; 17 (10): 1546-1552.
  44. Linch D.C., Yung L., Smith P. et al. Final analysis of the UKLG LY02 trial comparing 6-8 cycles of CHOP with 3 cycles of CHOP followed by a BEAM autograft in patients <65 years with poor prognosis histologically aggressive NHL: research paper. Br J Haematol 2010; 149 (2): 237-243.
  45. Kluin-Nelemans H.C., Zagonel V., Anastasopoulou A. et al. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized Advances in Hematology 9 phase III EORTC study. J National Cancer Institute 2001; 93 (1): 22-30.
  46. Verdonck L.F., Van Putten W.L.J., Hagenbeek A. et al. Comparison of chop chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin's lymphoma. New Engl J Med 1995; 332 (16): 1045-1051.
  47. Martelli M., Vignetti M., Zinzani P.L. et al. High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective randomized Italian multicenter study. J Clin Oncol 1996; 14 (2): 534-542.
  48. Haioun C., Lepage E., Gisselbrecht C. et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol - a groupe d'etude des lymphomes de l'adulte study. J Clin Oncol 2000; 18 (16): 3025-3030.
  49. Milpied N., Deconinck E., Gaillard F. et al. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. New Engl J Med 2004; 350 (13): 1287-1295.
  50. Менделеева Л.П., Савченко В.Г., Капланская И.Б., Любимова Л.С. Высокодозная полихимиотерапия с последующей аутотрансплантацией при лимфогранулематозе и лимфосаркомах. Матер. IV ежегод. Рос. онкол. конф. М 2000; 60.
  51. Stiff P.J., Unger J.M., Cook J. et al. Randomized phase III US/Canadian intergroup trial (SWOG S9704) comparing CHOP ± R for eight cycles to CHOP ± R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). J Clin Oncol 2011; 29 (suppl): 8001.
  52. Tarella C., Zanni M., Magni M. et al. Rituximab improves the efficacy of high-dose chemotherapy with autograft for high-risk follicular and diffuse large B-cell lymphoma: a multicenter Gruppo Italiano Terapie Innovative nei Linfomi survey. J Clin Oncol 2008; 26 (19): 3166-3175.
  53. Vitolo U., Chiappella A., Angelucci E. et al. Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B cell lymphoma with a poor prognosis: a phase II multicenter study. Haematologica 2009; 94 (9): 1250-1258.
  54. Dilhuydy M. S., Lamy T., Foussard C. et al. Front-line high dose chemotherapy with Rituximab showed excellent long term survival in adults with aggressive large B-cell lymphoma: final results of a phase II GOELAMS study. Biol Blood Marrow Transplant 2010; 16 (5): 672-677.
  55. Fitoussi O., Belhadj K., Mounier N. et al. Survival impact of rituximab combined with ACVBP and upfront consolidative autotransplantation in high risk diffuse large B-cell lymphoma for GELA. Haematologica 2011; 96: 1136-1143.
  56. Wilson W.H., Jung S.H., Porcu P. et al. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica 2012; 97 (5): 758-765.
  57. Wilson W.H., Dunleavy K., Pittaluga S. et al. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol 2008; 26: 2717-2724.
  58. Магомедова А.У., Кравченко С.К., Кременецкая А.М. и др. Девятилетний опыт лечения больных диффузной В-крупно­клеточной лимфосаркомой. Тер арх 2011; 7: 5-10.
  59. Hoelzer D., Hiddemann N., Baumann A. et al. High cure rate of adult Burkitt's and other high-grade NHL by the combination of short intensive chemotherapy cycles with rituximab. EHA 2007; abstract 410.
  60. Pfreundschuh M., Trümper L., Kloess M. et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood 2004; 104: 634-641.
  61. Gavrilina O., Zvonkov E., Gabeeva N. et al. High-dose chemotherapy with autologous stem cell transplantation in the treatment of patients with diffuse large B-cell lymphoma with bone marrow involvement. EBMT 2013; abstract 520.
  62. Pfreundschuh M., Ho A.D., Cavallin-Stahl E. et al. Prognostic significance of maximum tumor (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol 2008; 9: 435-444.
  63. Muller C., Murawski N., Wiesen M.H. et al. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood 2012; 119: 3276-3284.
  64. Sehn L.H., Scott D.W., Chhanabhai M. et al. Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 2011; 29: 1452-1457.
  65. Kasamon Y.L., Jones R.J., Piantadosi S. et al. High-dose therapy and blood or marrow transplantation for non-Hodgkin lymphoma with central nervous system involvement. Biol Blood Marrow Transplant 2005; 11 (2): 93-100.
  66. Hans C.P., Weisenburger D.D., Greiner T.C. et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103: 275-282.
  67. Choi W.W., Weisenburger D.D., Greiner T.C. et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res 2009; 15: 5494-5502.
  68. Gutierrez-García G., Cardesa-Salzmann T., Climent F. et al. Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood 2011; 117: 4836-4843.
  69. Barrans S., Crouch S., Smith A. et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol 2010; 28: 3360-3365.
  70. Savage K.J., Johnson N.A., Ben-Neriah S. et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood 2009; 114: 3533-3537.
  71. Aukema S.M., Siebert R., Schuuring E. et al. Double-hit B-cell lymphomas. Blood 2011; 117: 2319-2331.
  72. Johnson N., Slack G., Savage K. et al. Concurrent expression of MYC and BCL2 in R-CHOP treated diffuse large B cell lymphoma. J Clin Oncol 2012; 30 (28): 3452-3459.
  73. Schif B., Lennerz J.K., Kohler C.W. et al. SOCS1 mutation subtypes predict divergent outcomes in diffuse large B-cell lymphoma patients. Oncotarget 2013; 4 (1): 35-47.

Statistics

Views

Abstract - 105

Cited-By


Article Metrics

Metrics Loading ...

Refbacks

  • There are currently no refbacks.

Copyright (c) 2020 Gavrilina O.A., Gabeeva N.G., Morozova A.K., Sidorova A.A., Zvonkov E.E.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Novoslobodskaya str 31c4., Moscow, 127005, Russian Federation

Managing Editor:

 

© 2018 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies